PROJECT SUMMARY Background: Electronic cigarettes (e-cigarettes or ENDS) are battery-operated devices that generate an aerosol (called ?vapor?) that is inhaled by the user. Despite their increasing popularity and use worldwide, little is known about their health effects. There is concern that e-cigarettes expose users to metals, since a metal coil is used to generate the ?vapor?. Furthermore, most coils are composed of nickel and chromium, which are known inhalation carcinogens. A new e-cigarette type called POD is growing in popularity with unknown potential for exposure. Our goal is to evaluate how e-cigarette use patterns impact exposure to toxic metals. Specific Aims: 1) to understand the role of metal heating components on the transfer of metals into the aerosol, by analyzing metal concentrations in e-liquid before it is in contact with the heating coil, and in the aerosol generated, 2) to characterize patterns of e-cigarette use and other potential sources of metal exposures, and 3) to measure metals in blood, urine, saliva, and exhaled breath condensate (EBC) of e- cigarette users, non users, smokers and dual users, to evaluate how different patterns of e-cigarette and smoking use impact metal exposure. Preliminary studies: We have found nickel, chromium, and lead in aerosol from e-cigarettes, and also in urine, saliva and EBC of current e-cigarette users. All metal levels measured in the aerosol were higher than the metal levels found in e-liquid before contact with the coil. We also found that use behaviors, such as frequency of use and e-cigarette voltage, were associated with exposure levels. Design and setting: We will recruit men and women of all racial and ethnic backgrounds to one of five groups: 1) 50 MOD e-cigarette users, 2) 50 POD users, 3) 50 cigarette smokers, 4) 50 dual users (use e-cigarettes and combustible tobacco products), and 5) 50 non-users/smokers. Data collection: All participants will answer a questionnaire on smoking history, e-cigarette use patterns, and work/hobbies that may involve metal use. Samples of blood, urine, saliva, and exhaled breath will be collected to measure and compare metal levels within and between groups. For e-cigarette users, samples of their e-liquid before use, and vapor generated will be collected to understand the transfer of metals during e-cigarette use. Statistical Analysis: Linear regression models will be used to estimate the association of metals in biomarkers with e-cigarette use patterns, cotinine biomarkers, and metal concentrations in e-liquid and aerosol. For urine biomarkers, all models will be adjusted for urinary creatinine. Significance: The proposed project will allow us to evaluate e- cigarette users? exposure to metals, how their use patterns impact their metal exposures, and how their metal exposure levels compare to those of cigarette smokers, dual users, and non-users/smokers. This study will generate needed information to inform policy-level interventions for e-cigarette regulation as well as to plan future studies on the health effects of e-cigarette use.